Architecture and dynamics of the autophagic phosphatidylinositol 3-kinase complex

Baskaran, Sulochanadevi; Carlson, Lars-Anders; Stjepanovic, Goran; Young, Lindsey N.; Kim, Do Jin; Grob, Patricia; Stanley, Robin E.; Nogales, Eva; Hurley, James H.

doi:10.7554/elife.05115

Architecture and dynamics of the autophagic phosphatidylinositol 3-kinase complex

Journal Article · Tue Dec 09 00:00:00 EST 2014 · eLife

DOI:https://doi.org/10.7554/elife.05115· OSTI ID:1628829

Baskaran, Sulochanadevi ^[1]; Carlson, Lars-Anders ^[2]; ^[2]; Young, Lindsey N. ^[2]; Kim, Do Jin ^[2]; Grob, Patricia ^[3]; Stanley, Robin E. ^[4]; Nogales, Eva ^[5]; Hurley, James H. ^[6]

Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology; Univ. of California, Berkeley, CA (United States). California Inst. for Quantitative Biosciences; DOE/OSTI
Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology; Univ. of California, Berkeley, CA (United States). California Inst. for Quantitative Biosciences
Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology; Univ. of California, Berkeley, CA (United States). California Inst. for Quantitative Biosciences; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Division
National Institutes of Health (NIH), Bethesda, MD (United States). National Inst. of Diabetes and Digestive and Kidney Diseases. Lab. of Molecular Biology
Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology; Univ. of California, Berkeley, CA (United States). California Inst. for Quantitative Biosciences; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Division; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Division; Univ. of California, Berkeley, CA (United States). Howard Hughes Medical Inst.
Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology; Univ. of California, Berkeley, CA (United States). California Inst. for Quantitative Biosciences; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Division; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Division

The class III phosphatidylinositol 3-kinase complex I (PI3KC3-C1) that functions in early autophagy consists of the lipid kinase VPS34, the scaffolding protein VPS15, the tumor suppressor BECN1, and the autophagy-specific subunit ATG14. The structure of the ATG14-containing PI3KC3-C1 was determined by single-particle EM, revealing a V-shaped architecture. All of the ordered domains of VPS34, VPS15, and BECN1 were mapped by MBP tagging. The dynamics of the complex were defined using hydrogen–deuterium exchange, revealing a novel 20-residue ordered region C-terminal to the VPS34 C2 domain. VPS15 organizes the complex and serves as a bridge between VPS34 and the ATG14:BECN1 subcomplex. Dynamic transitions occur in which the lipid kinase domain is ejected from the complex and VPS15 pivots at the base of the V. The N-terminus of BECN1, the target for signaling inputs, resides near the pivot point. These observations provide a framework for understanding the allosteric regulation of lipid kinase activity.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1628829

Journal Information:: eLife, Journal Name: eLife Vol. 3; ISSN 2050-084X

Publisher:: eLife Sciences Publications, Ltd.Copyright Statement

Country of Publication:: United States

Language:: English

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Structural Biology and Electron Microscopy of the Autophagy Molecular Machinery Lai, Louis Tung Faat; Ye, Hao; Zhang, Wenxin Cells, Vol. 8, Issue 12 https://doi.org/10.3390/cells8121627	journal	December 2019
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Characterization of Atg38 and NRBF2, a fifth subunit of the autophagic Vps34/PIK3C3 complex Ohashi, Yohei; Soler, Nicolas; Ortegón, Miguel García Taylor & Francis https://doi.org/10.6084/m9.figshare.3830109.v1	text	January 2016
Structural insights into BCL2 pro-survival protein interactions with the key autophagy regulator BECN1 following phosphorylation by STK4/MST1 Lee, Erinna F.; Smith, Nicholas A.; Costa, Tatiana P. Soares Da Taylor & Francis https://doi.org/10.6084/m9.figshare.7547081	text	January 2019
Structural insights into BCL2 pro-survival protein interactions with the key autophagy regulator BECN1 following phosphorylation by STK4/MST1 Lee, Erinna F.; Smith, Nicholas A.; Costa, Tatiana P. Soares Da Taylor & Francis https://doi.org/10.6084/m9.figshare.7547081.v1	text	January 2019
Members of the autophagy class III phosphatidylinositol 3-kinase complex I interact with GABARAP and GABARAPL1 via LIR motifs Birgisdottir, Åsa Birna; Mouilleron, Stephane; Bhujabal, Zambarlal Taylor & Francis https://doi.org/10.6084/m9.figshare.7726157	text	January 2020
Members of the autophagy class III phosphatidylinositol 3-kinase complex I interact with GABARAP and GABARAPL1 via LIR motifs Birgisdottir, Åsa Birna; Mouilleron, Stephane; Bhujabal, Zambarlal Taylor & Francis https://doi.org/10.6084/m9.figshare.7726157.v1	text	January 2019
The stress-responsive kinases MAPKAPK2/MAPKAPK3 activate starvation-induced autophagy through Beclin 1 phosphorylation Wei, Yongjie; An, Zhenyi; Zou, Zhongju eLife, Vol. 4 https://doi.org/10.7554/elife.05289	journal	February 2015

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Journal Article · Sun Apr 14 20:00:00 EDT 2019 · Molecular Biology of the Cell · OSTI ID:1625250

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